Pediatric formula and methods for providing nutrition and improving tolerance

ABSTRACT

The present invention provides an improved pediatric formula and methods for providing nutrition to and enhancing tolerance in pediatric patients. The formula may be provided in powder, concentrate or ready-to-feed forms. The pediatric formula comprises, based on a 100 kcal basis, about 8 to about 16 grams carbohydrate (preferably about 9.4 to about 12.3 grams), about 3 to about 6 grams lipid (preferably about 4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein (preferably about 2.4 to about 3.3 grams), and a tolerance improver comprising a sufficient quantity for xanthum gum to produce a viscosity of no greater than about 200 centipoise ata pH of 4.0, or less The formula may also be provided in a powder. The formula preferably further comprises vitamins and minerals and may further comprise a stabilizer. The methods comprise administering to a pediatric patient an effective amount of a pediatric formula according to the invention, as described above.

CROSS REFERENCE

[0001] This application is a continuation-in-part of U.S. patentapplication Ser. No. 09/498,350 filed Feb. 4, 2000, now allowed which ishereby incorporated by reference.

FIELD OF THE INVENTION

[0002] The invention relates to a pediatric formula, and particularlyrelates to enhancing the tolerance of pediatric patients fed theformula. Pediatric patients include both infants (children 12 months ofage or less) and children (children more than 12 months of age but lessthan 13 yrs of age). (Therefore, all infants are children, but not allchildren will be infants.) More specifically, the invention is apediatric formula comprising xanthan gum that has been found effectivein increasing tolerance in patients fed such a formula. The invention isalso a method of providing nutrition and a method of improving tolerancecomprising administering an effective amount of a pediatric formulacomprising xanthan gum.

BACKGROUND OF THE INVENTION

[0003] Pediatric formulas may be classified into three general typesbased on the type of protein: intact protein-based, hydrolyzedprotein-based, and free amino acid-based. (Pediatric formulas encompassinfant formulas and formulas intended for children one year and older.)Commercial pediatric formulas may also contain, in addition to a proteinsource, carbohydrates, lipids, vitamins and minerals. Free amino acidsare currently utilized as the pediatric source in pediatric formulas(EleCare™, Ross Products Division of Abbott Laboratories) intended forchildren one year and older who have one or more of the following:problems digesting and absorbing regular foods, severe food allergies,gastrointestinal tract problems, or other conditions in which anelemental diet is needed.

[0004] Many pediatric patients experience intolerance to certainformulas (formula intolerance). The terms intolerance and formulaintolerance are used interchangeably herein. Intolerance is a non-immunesystem associated reaction and may be evidenced by behavior or stool orfeeding pattern changes such as increased spit-up or vomiting, anincreased number of stools, more watery stools, and increased fussinessas compared to normal infants who tolerate formula well. Intolerance ismost often indicated by gastrointestinal symptoms (e.g. emesis, stoolpatterns and gas) as well as behavioral characteristics (e.g. acceptanceof formula, fussing and crying). In clinical study settings suchbehavior may be cause for parents to remove their infants from aparticular study. Infants removed from a study because of such behaviorsare referred to as exits for intolerance. In a non-clinical setting suchbehavior often causes parents to switch formulas.

[0005] Intolerance can be contrasted with the allergic-type reactionssome infants exhibit to certain formulas. These allergic-type reactionsare immune system associated, and may be caused by the infant'ssensitivity to the protein present in the formula. Many infants whoexhibit allergies or sensitivities to intact (whole) proteins, such asthose in intact cow's milk protein or intact soy protein isolate-basedformulas, are able to tolerate extensively hydrolyzed protein.(Hydrolysate formulas (also referred to as semi-elemental formulas)contain protein that has been hydrolyzed or broken down into shortpeptide fragments and amino acids and as a result is more easilydigested by all infants.) These immune system associated allergies orsensitivities often result in cutaneous, respiratory or gastrointestinalsymptoms such as vomiting and diarrhea. Infants who exhibit reactions tointact protein formulas often will not react to hydrolysate formulasbecause their immune system does not recognize the hydrolyzed protein asthe intact protein that causes their symptoms. Infants who exhibitimmune system associated reactions to formulas may also exhibitnon-immune system associated reactions (formula intolerance), aspreviously described.

[0006] Many different pediatric formulas are in existence. Much of theprevious focus in the art has been on the physical stability of theformulas, and concurrent processing or manufacturing concerns.

[0007] U.S. Pat. No. 5,192,577 to Masson discloses and teaches the useof xanthan gum in a nutritional formula but only as a stabilizer andspecifically limits that use to formulas that use kappa carrageenan incombination with the xanthan gum. Masson deals primarily with thephysical stability of the nutritional formula disclosed therein and doesnot address the problem of intolerance exhibited by patients fed theformula.

[0008] U.S. Pat. No. 5,472,952 to Smidt et al. relates to nutritionallycomplete food compositions which contain partially hydrolyzed pectin forthe management of diarrhea. The use of xanthan gum as an emulsifier orstabilizer is disclosed but no teaching of the amount of xanthan gum isprovided.

[0009] U.S. Pat. No. 5,681,600 to Antinone et al. discloses use ofxanthan gum in a nutritional formula but teaches that such use ofxanthan gum is unacceptable because of unacceptable calcium deliveryresulting from use of formulas comprising xanthan gum.

[0010] U.S. Pat. No. 4,670,268 to Mahmoud discloses an enteralnutritional hypoallergenic nutritional formula which may contain xanthangum as a stabilizer but fails to provide any teaching of effectiveamounts of xanthan gum for that purpose.

[0011] U.S. Pat. No. 5,919,512 to Montezinos discloses the use ofxanthan gum as a stabilizer in a flavor/cloud emulsion such as ispresent in dilute juice and tea beverages. The emulsion disclosedtherein contains no protein and thus, would be unsatisfactory for use asa pediatric formula.

[0012] U.S. Pat. No. 5,597,595 to DeWille et al. discloses the use ofxanthan gum as an emulsion stabilizer in a low pH beverage fortifiedwith calcium and vitamin D.

[0013] U.S. Pat. No. 5,817,351 to DeWille et al. discloses the use ofxanthan gum as a stabilizer in low pH beverages that are calciumfortified. The beverages disclosed therein contain no fat and proteinand would be unsuitable as a complete nutritional source.

[0014] U.S. Pat. No. 5,609,897 to Chandler et al. discloses the use ofxanthan gum in a soft drink like powdered beverage that has beenfortified with calcium and vitamin D.

[0015] U.S. Pat. No. 5,858,449 to Crank et al. discloses the use ofxanthan gum in an isoflavone-enriched soy-based frozen dessert.

[0016] Past attempts to enhance the tolerance (especially to decreasespit-up) have often focused on significantly increasing the viscosity ofthe formula. Since spit-up is directly related to immaturity andgravity, increasing the viscosity of the infant formula has been shownto decrease spit-up. Vandenplas et al demonstrated a reduction inspit-up when the formula was thickened with carob bean gum. ClinicalPediatrics, Vol. 26, No. 2, (1987). Orenstein et al demonstrated thatinfant formula thickened with rice cereal reduced spit-up in infants.Journal of Pediatrics Volume 110, No. 2 (1987). Similar results withrice cereal were demonstrated by Ramenofsky et al, in Journal ofPediatric Surgery, 16:374 (1981) and Vanderhoof et al, in PediatricResearch 45:118A (1999).

SUMMARY OF THE INVENTION

[0017] The present invention provides an improved pediatric formula andmethods for providing nutrition and increasing the tolerance of childrenfed the formula. (As used herein, unless otherwise indicated, the termchildren is meant to encompass both infants and children over one yearin age. The terms child/children and pediatric patient are also usedinterchangeably.) The use of xanthan gum has provided unexpectedimprovements in tolerance. The formula may be in liquid concentrate,ready-to-feed or powdered form. The formula comprises, based on a 100kcal basis, about 8 to about 16 grams carbohydrate (preferably about 9.4to about 12.3 grams), about 3 to about 6 grams lipid (preferably about4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein(preferably about 2.4 to about 3.3 grams), and a tolerance improvercomprising about 37 to about 370 milligrams (preferably about 74 toabout 222 milligrams, more preferably about 111 to about 148 milligrams)xanthan gum. If the formula is provided in a powder form, it comprisesbased on 100 grams of powder, about 30 to about 90 grams carbohydrate(preferably about 48 to about 59 grams), about 15 to about 30 gramslipid (preferably about 20 to about 30), about 8 to about 17 gramsprotein (preferably about 10 to about 17 grams), and about 188 to about1880 milligrams (preferably about 375 to about 1125 milligrams, morepreferably about 565 to about 750 milligrams) xanthan gum.

[0018] The formula may further comprise a stabilizer and also preferablycomprises vitamins and minerals in amounts sufficient to supply thedaily nutritional requirements of infants or children over one. When theformula is an infant formula, the amounts of vitamins and minerals arepreferably selected according to FDA guidelines. When infants are fed aformula according to the invention, improved tolerance is exhibited bythose infants, as compared to infants fed a formula with the samecomposition but lacking the tolerance improver.

[0019] The invention also provides methods of providing nutrition to andimproving tolerance in a pediatric patient. The methods comprise feedingthe child an effective amount of a formula comprising, based on a 100kcal basis, about 8 to about 16 grams carbohydrate (preferably about 9.4to about 12.3 grams), about 3 to about 6 grams lipid (preferably about4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein(preferably about 2.4 to about 3.3 grams), and a tolerance improvercomprising about 37 to about 370 milligrams (preferably about 74 toabout 222 milligrams, more preferably about 111 to about 148 milligrams)xanthan gum. If the formula is provided in a powder form, it comprisesbased on 100 grams of powder, about 30 to about 90 grams carbohydrate(preferably about 48 to about 59 grams ), about 15 to about 30 gramslipid (preferably about 22 to about 28), about 8 to about 17 gramsprotein (preferably about 11 to about 17 grams), and about 188 to about1880 milligrams (preferably about 375 to about 1125 milligrams, morepreferably about 565 to about 750 milligrams) xanthan gum. Children fedformulas of the invention exhibit fewer symptoms of intolerance thanchildren fed the same formula but lacking the xanthan gum toleranceimprover.

[0020] A further advantage of the pediatric formulas of this inventionis that they can enhance tolerance with out significantly elevating theviscosity of the formula, especially when exposed to an acidicenvironment such as the stomach. The formula, when diluted for pediatricconsumption, will have a viscosity of about 200 centipoise or less, whenexposed to a pH of about 4.0 or less.

DETAILED DESCRIPTION OF THE INVENTION

[0021] The present invention provides an improved pediatric formula thatreduces the intolerance of children fed the formula. The invention alsoprovides methods for providing nutrition to and improving tolerance inpediatric patients comprising feeding a formula of the invention. Theuse of xanthan gum has provided unexpected improvements in tolerance.

[0022] Intolerance (formula intolerance) in infants is often indicatedby gastrointestinal symptoms (e.g. emesis, stool patterns, and gas) aswell as behavioral characteristics (e.g. acceptance of formula, fussing,and crying). For purposes of this invention, improved tolerance (orreduced intolerance) is defined as an improvement (change towards normalpatterns) of one or more of the following symptoms or characteristics:stool pattern, vomiting, spit up, acceptance of formula, fussing,crying, or exits for intolerance (clinical setting).

[0023] The pediatric formula of the invention may be provided inpowdered, liquid concentrate or ready-to-feed forms. Before feeding,water is added to both the powdered and concentrate forms of theformula. In a first embodiment, a pediatric formula of the inventioncomprises, based on a 100 kcal basis, about 8 to about 16 gramscarbohydrate (preferably about 9.4 to about 12.3 grams), about 3 toabout 6 grams lipid (preferably about 4.7 to about 5.6 grams), about 1.8to about 3.3 grams protein (preferably about 2.4 to about 3.3 grams),and a tolerance improver comprising about 37 to about 370 milligrams(preferably about 74 to about 222 milligrams, more preferably about 111to about 148 milligrams) xanthan gum. If provided in a powder form, theformula comprises, based on 100 grams of powder, about 30 to about 90grams carbohydrate (preferably about 48 to about 59 grams ), about 15 toabout 30 grams lipid (preferably about 22 to about 28), about 8 to about17 grams protein (preferably about 11 to about 17 grams), and about 188to about 1880 milligrams (preferably about 375 to about 1125 milligrams,more preferably about 565 to about 750 milligrams) xanthan gum. Asummary of the carbohydrate, lipid and protein ranges (on a per 100 kcalbasis, per 100 grams powder basis and per liter basis (as fedconcentration) for a formula according to the invention is provided inTable I.

[0024] As noted immediately above, the quantity of xanthan gum that isutilized in the pediatric formula can vary widely. In a more preferredembodiment, an appropriate quantity of xanthan gum is utilized tomaintain the viscosity of the formula at a level of no greater thanabout 200 centipoise, especially when exposed to acidic conditions (i.e. a pH of 4.0 or less). In one embodiment, the viscosity of theformula is no greater than about 15 175 centipoise, at a pH of 4.0 orless. In a second embodiment, the viscosity of the formula is no greaterthan about 125 centipoise, more preferably no greater than about 100centipoise, even more preferably no greater than about 75 centipoise,and in a further embodiment has a viscosity of no greater than about 50centipoise, all at a pH of 4.0 or less.

[0025] Xanthan gum is a high molecular weight polysaccharide produced byfermentation of a carbohydrate by Xanthomonas campestris. While xanthangum is available in various mesh sizes, the use of xanthan gum in thisinvention is not limited to any particular mesh size. An appropriatemesh size may be selected based on processing parameters, e,g., a finermesh size (200 mesh) may be preferred if the xanthan gum is to be dryblended into a formula whereas, a more coarse size (80 mesh) may bepreferred if the xanthan gum is not dry blended into a formula. Asuitable xanthan gum for use in this invention is Keltrol F Xanthan Gum(200 mesh) available from CP Kelco, of San Diego, Calif. or from ArcherDaniels Midland of Decatur, Ill.

[0026] Suitable carbohydrates, lipids and proteins can vary widely andare well known to those skilled in the art of making pediatric formulas.Suitable carbohydrates may thus include, but are not limited to,hydrolyzed, intact, naturally and/or chemically modified starchessourced from corn, tapioca, rice or potato in waxy or non waxy forms;and sugars such as glucose, fructose, lactose, sucrose, maltose, highfructose corn syrup, and mixtures thereof. Maltodextrins arepolysaccharides obtained from the acid or enzyme hydrolysis of starchessuch as those from corn or rice. Their classification is based on thedegree of hydrolysis and is reported as dextrose equivalent (DE). Whenprotein hydrolysates are the protein source, the DE of any maltodextrinutilized is preferably less than about 18-20. When protein hydrolysatesare the protein source it is also preferable to avoid conditions whichcould lead to the formation of excessive Maillard browning products.

[0027] Suitable lipids include, but are not limited to, coconut oil, soyoil, corn oil, olive oil, safflower oil, high oleic safflower oil, MCToil (medium chain triglycerides), sunflower oil, high oleic sunfloweroil, palm oil, palm olein, canola oil, lipid sources of arachidonic acidand docosahexaneoic acid, and mixtures thereof. Lipid sources ofarachidonic acid and docosahexaneoic acid include, but are not limitedto, marine oil, egg yolk oil, and fungal oil.

[0028] Suitable protein sources include milk, soy, rice, meat (e.g.,beet, animal and vegetable (e.g., pea, potato), egg (egg albumen),gelatin, and fish. Suitable intact proteins include, but are not limitedto, soy based, milk based, casein protein, whey protein, rice protein,beef collagen, pea protein, potato protein and mixtures thereof.Suitable protein hydrolysates also include, but are not limited to, soyprotein hydrolysate, casein protein hydrolysate, whey proteinhydrolysate, rice protein hydrolysate, potato protein hydrolysate, fishprotein hydrolysate, egg albumen hydrolysate, gelatin proteinhydrolysate, a combination of animal and vegetable protein hydrolysates,and mixtures thereof. Hydrolyzed proteins (protein hydrolysates) areproteins that have been hydrolyzed or broken down into shorter peptidefragments and amino acids. Such hydrolyzed peptide fragments and freeamino acids are more easily digested. In the broadest sense, a proteinhas been hydrolyzed when one or more amide bonds have been broken.Breaking of amide bonds may occur unintentionally or incidentally duringmanufacture, for example due to heating or shear. For purposes of thisinvention, the term hydrolyzed protein means a protein which has beenprocessed or treated in a manner intended to break amide bonds.Intentional hydrolysis may be effected, for example, by treating anintact protein with enzymes or acids. The hydrolyzed proteins that arepreferably utilized in formulas according to this invention arehydrolyzed to such an extent that the ratio of the amino nitrogen (AN)to total nitrogen (TN) ranges from about 0.1 AN to 1.0 TN to about 0.4AN to about 1.0 TN, preferably about 0.25 AN to 1.0 TN to about 0.4 ANto about 1.0 TN. (AN:TN ratios given are for the hydrolysate proteinsource alone, and do not represent the AN:TN ratio in the finalpediatric nutritional formula product, since free amino acids may beadded as a supplement and would alter the reported value.) Protein mayalso be provided in the form of free amino acids. A formula according tothe invention is preferably supplemented with various free amino acidsin order to provide a more nutritionally complete and balanced formula.Examples of suitable free amino acids include, but are not limited to,L-tryptophan, L-tyrosine, L-cystine, L-taurine, L-methionine,L-arginine, and L-carnitine.

[0029] A formula of the invention preferably also contains vitamins andminerals in an amount designed to supply the daily nutritionalrequirements of a pediatric patient. The formula preferably includes,but is not limited to, the following vitamins and minerals: calcium,phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc,selenium, iodine, and Vitamins A, E, C, D, K and the B complex. Furthernutritional guidelines for infant formulas can be found in the InfantFormula Act, 21 U.S.C. section 350(a). The nutritional guidelines foundin the Infant Formula Act continue to be refined as further researchconcerning infant nutritional requirements is completed. This inventionis intended to encompass formulas containing vitamins and minerals thatmay not currently be listed in the Act.

[0030] In a second embodiment of the invention, the invention formulafurther comprises a stabilizer. Suitable stabilizers for use inpediatric nutritional formulas are well known to those skilled in theart. Suitable stabilizers include, but are not limited to, gum arabic,gum ghatti, gum karaya, gum tragacanth, agar, furcellaran, guar gum,gellan gum, locust bean gum, pectin, low methoxyl pectin, gelatin,microcrystalline cellulose, CMC (sodium carboxymethylcellulose),methylcellulose hydroxypropyl methyl cellulose, hydroxypropyl cellulose,DATEM (diacetyl tartaric acid esters of mono- and diglycerides),dextran, carrageenans, and mixtures thereof. A formula according to theinvention preferably is free of kappa carrageenan as a stabilizer, andmost preferably is free of a carrageenan. A formula is defined as beingfree of kappa carrageenan if any carrageenan utilized is predominatelyin another form (iota or lambda). For purposes of this invention, freeof kappa carrageenan or free of carrageenan means that no kappacarrageenan or carrageenan is added during manufacturing. The amount ofstabilizers utilized will vary depending upon the stabilizer(s)selected, the other ingredients present, and the stability and viscosityof the formula that is sought. Appropriate amounts can be determined bythose of skill in the art based on the particular characteristics (e.g.,viscosity) being sought in the formula.

[0031] The invention also provides methods of providing nutrition to andimproving tolerance in a pediatric patient. The methods comprise feedingthe child an effective amount of a formula comprising, based on a 100kcal basis, about 8 to about 16 grams carbohydrate (preferably about 9.4to about 12.3 grams), about 3 to about 6 grams lipid (preferably about4.7 to about 5.6 grams), about 1.8 to about 3.3 grams protein(preferably about 2.4 to about 3.3 grams), and a tolerance improvercomprising about 37 to about 370 milligrams (preferably about 74 toabout 222 milligrams, more preferably about 111 to about 148 milligrams)xanthan gum. If the formula is provided in a powder form, it comprisesbased on 100 grams of powder, about 30 to about 90 grams carbohydrate(preferably about 48 to about 59 grams ), about 15 to about 30 grams fat(preferably about 22 to about 28), about 8 to about 17 grams protein(preferably about 11 to about 17 grams), and about 188 to about 1880milligrams (preferably about 375 to about 1125 milligrams, morepreferably about 565 to about 750 milligrams) xanthan gum.

[0032] In another embodiment, the formula may further comprise astabilizer. Either embodiment also preferably comprises vitamins andminerals, in amounts as discussed above. Suitable carbohydrates, lipids,proteins or proteins, and stabilizers are well known to those skilled inthe art and may include, but are not limited to, the substancesdescribed above. Preferably, if the formula is an infant formula, themethod comprises feeding a sufficient amount of the formula to fulfillall of the infant's daily nutritional requirements.

[0033] The pediatric formulas of this invention can be manufacturedusing techniques well known to those skilled in the art. Variousprocessing techniques exist for producing powdered, ready-to-feed andconcentrate liquid formulas. Typically, these techniques includeformation of a slurry from one or more solutions which may contain waterand one or more of the following: carbohydrates, proteins, lipids,stabilizers, vitamins and minerals. This slurry is emulsified,homogenized and cooled. Various other solutions may be added to theslurry before processing, after processing or at both times. Theprocessed formula is then sterilized and may be diluted to be utilizedon a ready-to-feed basis or stored in a concentrated liquid or a powder.If the resulting formula is meant to be a ready-to-feed liquid orconcentrated liquid, an appropriate amount of water would be addedbefore sterilization. If the resulting formula is meant to be a powder,the slurry will be heated and dried to obtain a powder. The powderresulting from drying may be dry blended with further ingredients, ifdesired.

[0034] Viscosity is the ratio of shear stress to shear rate, expressedas dynes-second/cm², or poise. A centripoise is one hundredth of apoise. A poise is a unit of coefficient of viscosity, defined as thetangential force per unit area required to maintain one unit differencein velocity between two parallel planes separated by one centimeter offluid.

[0035] Any viscosity determination should be carried out on a samplethat has been diluted to a concentration suitable for consumption by aninfant (about 20 calories per ounce). The sample should be at roomtemperature at the time of testing. If reconstituted, the sample shouldbe allowed to sit 30 minutes prior to testing (to allow hydration of theXanthum gum). The viscosity is determined using a Brookfield (modelDVII+) viscometer with a #1 spindle. The viscosity is measured byoperating the viscometer at a spindle speed of 30 rpm, or the highestspeed possible to obtain a reading that is on scale.

[0036] The following examples are illustrative of the methods andcompositions of the invention for improving tolerance in pediatricpatients. While the invention is described in terms of a powdered infantnutritional formula in the examples, below, it is not intended to be solimited, as it is intended to encompass both ready-to-feed andconcentrate liquid infant formulas as well as formulas for children oneyear in age or older. The examples are not intended to be limiting asother carbohydrates, lipids, proteins, stabilizers, vitamins andminerals may be used without departing from the scope of the invention.

EXAMPLE 1

[0037] Clinical Study

[0038] Following is a summary of the results of a clinical study ontolerance where infants were fed one of four different formulas. Threedifferent formulas of the invention and a control formula (identical butlacking the xanthan gum tolerance improver) were utilized.

[0039] The masked, randomized, parallel tolerance study was conducted onhealthy, term infants, 28 days or less in age. The infants were fedcommercially-labeled Alimentum_Protein Hydrolysate Formula With Iron(Ross Products Division, Abbott Laboratories) in a ready-to-feedcomposition, for one week as a baseline. Immediately thereafter, theyrandomly received either a control formula or one of formulas B, C or D.The composition of the control formula was identical to that of formulasB-D, except for the presence of differing amounts of xanthan gum in theformulas B-D. The composition of all four formulas is provided in TablesII and II A. The control and formulas B-D were provided in powdered formin metal cans of sufficient size to contain 350 grams.

[0040] Infants were eligible for the study if they were judged to be ingood health; were full-term with a gestational age of 37 to 42 weeks;had a birth weight greater than 2500 g; were at least 28 days of age;were exclusively formula fed at the time of the study; had parents whovoluntarily signed an informed consent form; had parents who agreed notto administer mineral or vitamin supplements; had parents who agreed tofeed their infant only the study formula for the duration of the study;were the product of a single birth pregnancy; did not have a maternalmedical history which may have adversely affected the fetus such asdiabetes, tuberculosis, perinatal infections, or substance abuse; didnot show evidence of cardiac, respiratory, gastrointestinal,hematological, or metabolic disease; and did not have a birth weightgreater than the 95th percentile (NCHS (National Center for HealthStatistics)) for infants whose mothers had gestational diabetes.

[0041] Infants were identified by the investigators from the localpopulation, and eligible infants were recruited. A total of 182 infants,from three different sites, were enrolled in the study. Of the initial182, 45 exited during the baseline period and never received the controlor formulas B-D. Of the 137 who received either the control or one ofthe formulas B-D, 12 infants failed to complete the study.

[0042] Day one of the study was defined as the day of enrollment intothe study. On day one, demographic/entrance data was collected andinfants were weighed unclothed. Parents received approximately twelve32-fl oz cans of the baseline Alimentum Protein Hydrolysate Formula WithIron in a ready to feed composition. Parents were instructed to continuefeeding their current formula until 6:00 p.m. on day one, and then tobegin feeding the baseline formula on the first feed after 6:00 p.m onday one. Intake and stool data were collected beginning on day one at6:00 p.m. and ending at 5:59 p.m. on day seven. Parents also recordedthe characteristics of their infants stools, volume of formula consumedat each feeding and incidence of spit up and vomiting.

[0043] On day eight of the study, records completed by parents werereviewed by study personnel for completeness and accuracy, infants werereweighed and questionnaires regarding formula satisfaction and feedingand stool patterns were completed by the parents. Parents returnedunused baseline formula and were given approximately four cans of one ofthe assigned formulas the control, B, C or D. Parents were instructed tocontinue feeding the baseline formula until 6:00 p.m. on day eight, andto begin feeding the assigned formula thereafter and record feeding andstool information. Intake and stool data were collected from day eightstarting at 6:00 p.m. and ending at 5:59 p.m. on study day fourteen. Sixdays of data were collected on the control and formulas B-D. As with thebaseline feedings, the dietary intake and stool records completed byparents during days eight to fourteen were reviewed by study personnelat a visit on day fifteen.

[0044] On day fifteen, infants were weighed, questionnaires werecompleted and parents returned any unused portions of the formulas.

[0045] Statistical Analysis

[0046] Primary variables were average daily stool number, mean rankstool consistency and incidence of vomiting and spit up. The primaryanalysis consisted of an analysis of the primary outcome variables on anintent-to-treat basis. The secondary analysis was conducted with studycompleters. The study period data were analyzed using one-way analysisof variance with site as blocking factor. Additionally, an analysis ofcovariance with study period data as response, and baseline data ascovariate was done as a confirmatory analysis. Transformations (rankingarcsine of the square root) were applied when appropriate.Categorical/ordinal data were analyzed using contingency table methods.All tests were two-sided and performed at the 0.05 significance level.The significance level in the three primary analysis was adjusted formultiplicity of testing using Holm's stepdown Bonferroni method.

[0047] Results

[0048] No statistically significant differences were observed inethnicity or age on study day one. Significant differences were observedin gender distribution among groups at entry. (P<0.05). Weight at dayone was significantly greater in the group fed formula B, compared tothe group fed the control formula on day one. Significantly more infantsfed the control formula exited due to intolerance than compared to thosereceiving formulas B, C or D (those containing the xanthan gum toleranceimprover).

[0049] Statistically significant differences were observed among groupsin the average daily number of stools (P=0.003 adjusted formultiplicity). Infants fed the control formula passed significantly morestools than compared to infants fed formulas B (P=0.0001) and D(P=0.0073). Infants fed the control formula passed a mean of 2.7±0.2stools per day and infants fed formula B and D passed a mean of 1.6±0.2and 2.1±0.3 stools per day during the experimental period (days 8-14).There were no statistically significant differences among groups in meanrank stool consistency. The percent of stools which were watery weresignificantly different among groups. Infants fed the control formulahad significantly more stools which were watery compared to the formulaC and D groups (P<0.01) when baseline measurements were added ascovariate in the analysis. No other significant differences wereobserved among groups for other stool parameters (loose/mushy, soft,formed). Results on daily number of stools, mean rank stool consistency,watery, loose/mushy stools, soft stools and formed stools are reportedin Table III.

[0050] No statistically significant differences were observed amonggroups in the percent of feedings with spit up or the percent offeedings with vomiting. No statistically significant differences wereobserved in the number of feedings per day, intakes in ml per day, orintakes in ml per kg per day among groups. Results on spit ups,vomiting, feedings per day, intakes in ml per day and intakes in ml perkg per day are reported in Table IV.

[0051] No significant differences were observed among groups in weightNCHS Z-scores at day fifteen, or weight gain during the experimentalperiod (days 8-14). A significant difference was observed among groupsin weight of infants at the day 15 visit. Infants fed formula B weresignificantly heavier than infants fed the control formula (P<0.01) asthey had been at day one. When day eight weight was used as a covariate,no significant differences were observed among groups in the weight atthe end of the study. Results are reported in Table V.

[0052] Discussion

[0053] The results of the study confirmed that the addition of xanthangum to a formula improved the tolerance of infants fed such a formula.Infants fed formulas B, C and D (with xanthan gum tolerance improver)generally passed fewer stools per day than those fed the control formula(Table II). Corroborative results found that infants fed formulas B, Cand D were judged by parents to have fewer days with too many stoolscompared to those fed the control formula. In addition, the number ofinfants exiting due to formula intolerance was significantly lower inthe groups fed formulas B, C and D compared to the group fed the controlformula. Results are shown in Table VI. The percentage of exits for thegroup fed the control formula, with no tolerance improver, was 22%.Thus, the reduction in exits (0-6%) for infants fed formulas B, C and Dwere clinically striking compared to the control. While the infantsenrolled in this study were healthy infants (with no known allergy orsensitivity to intact proteins), the improved tolerance results achievedhere should also be experienced by infants with allergies orsensitivities to intact proteins who exhibit symptoms of intolerancewhile on current hydrolysate formulas and by children over one whoexhibit symptoms of intolerance.

EXAMPLE 2

[0054] A powdered formula is prepared by solubilizing approximately 6870lb. corn maltodextrin, 3095 lb. sucrose, 24.4 kg magnesium chloride,54.9 kg potassium citrate, 17.8 kg sodium chloride, 114.5 kg calciumphosphate, tribasic, 25.5 kg calcium carbonate, 16.4 kg potassiumchloride and 13.7 g potassium iodide in water at 160° F. to make anaqueous solution. The amount of water used in making the aqueoussolution will be optimized for the particular manufacturing equipmentutilized. This solution is blended with a second solution containing1911 lb. MCT oil, 130.6 kg diacetyl tartaric acid esters of mono- anddiglycerides, 26.1 kg mono- and diglycerides, 2020 lb. high oleicsafflower oil, 1.1 lb. mixed tocopherols, 1613 lb. soy oil, 2.1 kgascorbyl palmitate and 3.2 kg of a vitamin premix containing vitamin Apalmitate, vitamin E acetate, phylloquinone and vitamin D3 to form aslurry. This slurry is mixed for a minimum of 30 minutes up to two hoursat a temperature of 68 to 74° C. This slurry is emulsified at 1000 psi,homogenized through a two-stage homogenizer at 2500 psi/500 psi andcooled through a plate heat exchanger to approximately 4° C. Solutionscontaining free amino acids, water soluble vitamins and trace mineralsare added to the processed slurry. The slurry is heated to 74.4 to 85°C. for a minimum of 16 seconds and spray dried to obtain a powder havinga moisture content of approximately 1.5%. The spray dried powder is dryblended with approximately 3430 lb. casein hydrolysate and 51.2 kg ofxanthan gum.

EXAMPLE 3

[0055] A powdered formula is prepared by solubilizing approximately 6870lb. corn maltodextrin, 3095 lb. sucrose, 24.4 kg magnesium chloride,54.9 kg potassium citrate, 17.8 kg sodium chloride, 114.5 kg calciumphosphate, tribasic, 25.5 kg calcium carbonate, 16.4 kg potassiumchloride and 13.7 g potassium iodide in water at 160° F. to make anaqueous solution. The amount of water used in making the aqueoussolution will be optimized for the particular manufacturing equipmentutilized. This solution is blended with a second solution containing1911 lb. MCT oil, 130.6 kg diacetyl tartaric acid esters of mono- anddiglycerides, 26.1 kg mono- and diglycerides, 2020 lb. high oleicsafflower oil, 1.1 lb. mixed tocopherols, 1613 lb. soy oil, 2.1 kgascorbyl palmitate and 3.2 kg of a vitamin premix containing vitamin Apalmitate, vitamin E acetate, phylloquinone and vitamin D3 to form aslurry. This slurry is mixed for a minimum of 30 minutes up to two hoursat a temperature of 68 to 74° C. This slurry is emulsified at 1000 psi,homogenized through a two-stage homogenizer at 2500 psi I 500 psi andcooled through a plate heat exchanger to approximately 4° C.Approximately 3430 lb. casein hydrolysate is blended in water for aminimum of 30 minutes up to two hours at a temperature of 68-74° C. Thisslurry is emulsified at 1000 psi, homogenized through a two-stagehomogenizer at 2500 psi/500 psi, cooled through a plate heat exchangerto approximately 4° C. and added to the carbohydrate/fat/lipid blend.Solutions containing free amino acids, water soluble vitamins and traceminerals are added to the processed slurry. The slurry is heated to 74.4to 85° C. for a minimum of 16 seconds and spray dried to obtain a powderhaving a moisture content of approximately 1.5%. The spray dried powderis dry blended with 51.2 kg of xanthan gum.

EXAMPLE 4

[0056] A powdered formula is prepared by solubilizing approximately 6870lb. corn maltodextrin, 3095 lb. sucrose, 24.4 kg magnesium chloride,54.9 kg potassium citrate, 17.8 kg sodium chloride, 114.5 kg calciumphosphate, tribasic, 25.5 kg calcium carbonate, 16.4 kg potassiumchloride and 13.7 g potassium iodide in water at 160° F. to make anaqueous solution. The amount of water used in making the aqueoussolution will be optimized for the particular manufacturing equipmentutilized. This solution is blended with a second solution containing1911 lb. MCT oil, 130.6 kg diacetyl tartaric acid esters of mono- anddiglycerides, 26.1 kg mono- and diglycerides, 2020 lb. high oleicsafflower oil, 1.1 lb. mixed tocopherols, 1613 lb. soy oil, 2.1 kgascorbyl palmitate, 3.2 kg of a vitamin premix containing vitamin Apalmitate, vitamin E acetate, phylloquinone and vitamin D3 and thexanthan gum to form a slurry. This slurry is mixed for a minimum of 30minutes up to two hours at a temperature of 68 to 74° C. This slurry isemulsified at 1000 psi, homogenized through a two-stage homogenizer at2500 psi/500 psi and cooled through a plate heat exchanger toapproximately 4° C. Approximately 3430 lb. casein hydrolysate is blendedin water for a minimum of 30 minutes up to two hours at a temperature of68-74° C. This slurry is emulsified at 1000 psi, homogenized through atwo-stage homogenizer at 2500 psi/500 psi, cooled through a plate heatexchanger to approximately 4° C. and added to the carbohydrate/fat/lipidblend. Solutions containing free amino acids, water soluble vitamins andtrace minerals are added to the processed slurry. The slurry is heatedto 74.4 to 85° C. for a minimum of 16 seconds and spray dried to obtaina powder having a moisture content of approximately 1.5%.

EXAMPLE 5

[0057] A powdered formula is prepared by solubilizing approximately 6870lb. rice maltodextrin, 3095 lb. sucrose, 24.4 kg magnesium chloride,54.9 kg potassium citrate, 17.8 kg sodium chloride, 114.5 kg calciumphosphate, tribasic, 25.5 kg calcium carbonate, 16.4 kg potassiumchloride and 13.7 g potassium iodide in water at 160° F. to make anaqueous solution. This solution is blended with a second solutioncontaining 1911 lb. MCT oil, 130.6 kg diacetyl tartaric acid esters ofmono- and diglycerides, 26.1 kg mono- and diglycerides, 2020 lb higholeic safflower oil, 1.1 lb. mixed tocopherols, 1613 lb. soy oil, 2.1 kgascorbyl palmitate and 3.2 kg of a vitamin premix containing vitamin Apalmitate, vitamin E acetate, phylloquinone and vitamin D3. to form aslurry. This slurry is mixed for a minimum of 30 minutes up to two hoursat a temperature of 68 to 74° C. This slurry is emulsified at 1000 psi,homogenized through a two-stage homogenizer at 2500 psi/500 psi andcooled through a plate heat exchanger to approximately 4° C. Solutionscontaining water soluble vitamins and trace minerals are added to theprocessed slurry. The slurry is heated to 74.4 to 85° C. for a minimumof 16 seconds and spray dried to obtain a powder having a moisturecontent of approximately 1.5%. The spray dried powder is dry blendedwith approximately 3430 lb. whey protein hydrolysate, free amino acids,41.2 kg locust bean gum and 51.2 kg of xanthan gum.

EXAMPLE 6

[0058] The following viscosity determinations were carried out.

[0059] Three different infant formulas were subjected to testing. Thefirst formula contained xanthan gum (750mg/liter when reconstituted) andwas produced using methods analogous to those described in Example 3 ofthe '350 patent application (clinical batch #P99-TR1/Exp Jan. 1, 2003).

[0060] The second formula (B) also contained xanthan gum (750mg/literwhen reconstituted). A sample of Similac powder was removed from a lotproduced for commercial sale ( Lot # 75257RE/Exp Apr. 3, 2004). 51.4grams of this formula was dry blended with 300 mg of xanthan gum.

[0061] The third infant formula (C) is representative of those describedby U.S. Pat. No. 6,099,871 (Martinez). The formula was Enfamil AR and itwas purchased in Columbus, Ohio (Lot # MMC06/Exp Jan. 1, 2002). EnfamilAR contains waxy rice starch, like those of the Martinez reference (seepage 19 of Exhibit A, Enfamil AR manufacturer's brochure).

[0062] Testing Conditions

[0063] Formula A and Formula B were reconstituted with warm tap water toachieve a concentration of 20 calories per fluid ounce and was allowedto stand at least 30 minutes prior to testing. Formula C was purchasedas a ready-to-feed liquid, having a concentration of 20 calories perfluid ounce. This value corresponds to the concentration that would beutilized to feed a normal infant.

[0064] Viscosity readings for the three formulas were determined at roomtemperature, on a Brookfield viscometer (Model DVII+) at a speed of 30rpm, using a #1 spindle. The initial reading was determined withoutmodifying the pH of the infant formula.

[0065] After the initial viscosity reading, additional viscosityreadings were taken while the pH of the infant formula was graduallylowered. Hydrochloric acid (6 molar) was utilized to produce an acidicpH.

[0066] Testing Results

[0067] Table 1-3 below summarize the results that were obtained: TABLE 1(Invention) Product A pH HCl (ml)* Viscosity (cp) Temperature (° F.) RPM5.82 0.0 11.8 76.9 30 5.63 0.1 12.8 75.8 30 5.27 0.2 13.4 75.2 30 4.990.5 13.4 74.9 30 4.70 0.7 14.0 74.5 30 4.33 1.2 15.4 74.2 30 3.78 2.234.2 74.2 30 3.32 3.5 53.4 73.8 30

[0068] TABLE 2 (Invention) Product B pH HCl (ml)* Viscosity (cp)Temperature (° F.) RPM 6.69 0.0 11.4 75.8 30 5.66 0.4 12.6 74.3 30 5.290.8 21.6 74.0 30 4.98 1.2 29.6 73.8 30 4.64 1.6 1.8 73.6 60 4.25 2.0 2.272.7 60 3.68 2.5 3.8 72.2 30 3.28 2.8 3.4 72.4 30

[0069] TABLE 3 (Prior Art) Product C pH HCl (ml)* Viscosity (cp)Temperature (° F.) RPM¹ 6.65 0.0 50.8 72.4 30 6.07 0.2 52.4 71.6 30 5.600.5 62.8 71.6 30 5.28 0.6 65.2 71.3 30 5.00 0.9 113.4 71.3 30 4.67 1.2453.5 71.1 12 4.30 1.6 1862 71.1 3 3.65 2.1 809 70.9 6 3.30 2.4 160.270.9 30

EXAMPLE 7

[0070] The testing procedure of Example 6 was repeated except that theconcentration of xanthan gum was varied as shown below. The pediatricformula was produced using methods analagous to Example 3 It scomposition was also analagous to that of Example 3, except for thequantity of xanthan gum which was varied as depicted below. TABLE 4 1000mg/L Xanthan Gum Sample Cumulative Temperature PH 6 M HCl (ml) Viscosity(cp) (° F.) RPM 5.86 0 70.0 73.4 30 5.56 0.1 69.6 73.4 30 5.23 0.3 70.273.1 30 4.97 0.5 71.6 72.9 30 4.70 0.8 74.6 72.7 30 4.31 1.3 79.8 72.530 3.82 2.3 100.6 72.5 30 3.32 3.6 111.8 72.5 30 2.84 5.3 97.8 72.5 30

[0071] TABLE 5 1500 mg/L Xanthan Gum Sample Cumulative Temperature pH 6M HCl (ml) Viscosity (cp) (° F.) RPM 5.85 0 132.2 75.1 30 5.63 0.1 131.873.8 30 5.26 0.3 130.2 73.8 30 4.88 0.6 131.6 73.6 30 4.67 0.9 134.473.4 30 4.33 1.4 141.2 73.2 30 3.80 2.3 163.6 73.1 30 3.28 3.8 163.673.1 30

[0072] While the invention has been described herein with reference toparticular embodiments, it is to be understood that it is not intendedto limit the invention to the specific forms disclosed. On the contrary,it is intended to cover all modifications and alternative forms fallingwithin the spirit and scope of the invention. TABLE 6 RANGES OFCARBOHYDRATE, LIPID AND PROTEIN PER 100 KCAL, PER 100 GRAMS POWDER ANDPER LITER (AS FED CONCENTRATION) Per 100 grams Per liter (as fedNutrient (g) Range Per 100 kcal powder concentration) Carbo- Broadest 8-16 30-90  53-107 hydrate Preferred  9.4-12.3 48-59 64-83 LipidBroadest 3-6 15-30 22-40 Preferred 4.7-5.6 22-28 32-38 Protein Broadest1.8-3.3  8-17 12-22 Preferred 2.4-3.3 11-17 16-22

[0073] TABLE 7 NUTRIENT CONTENT OF CONTROL AND FORMULAS B, C, AND D*Nutrient¹ Per Liter Per 100 kcal Per 100 g Powder Protein (g) 18.6 2.7513.9 Fat (g) 37.5 5.55 28.1 Carbohydrate (g) 73 10.8 54.6 Calcium (mg)710 105 531 Phosphorus (mg) 507 75 379 Magnesium (mg) 51 7.5 38.1 Iron(mg) 12.2 1.8 9.1 Zinc (mg) 5 0.74 3.7 Manganese (mcg) 34 5 25 Copper(mcg) 500 74 374 Iodine (mcg) 100 14.8 75 Sodium (mg) 297 43.9 222Potassium (mg) 800 118.3 598 Chloride (mg) 541 80 405 Selenium (mcg) 162.4 12 Vitamin A (IU) 2,200 325 1.646 Vitamin D (IU) 400 59 299 VitaminE (IU) 20.8 3.1 15.6 Vitamin K₁ (IU) 101 14.9 75.5 Thiamin (mcg) 580 86434 Riboflavin (mcg) 600 89 449 Vitamin B-6 (mcg) 530 78 396 VitaminB-12 (mcg) 3 0.44 2.24 Niacin (mg) 9 1.33 6.73 Folic Acid (mcg) 100 14.874.8 Panthothenic Acid 5 0.74 3.74 (mg) Biotin (mcg) 30 4.4 22.4 VitaminC (mg) 90 13.3 67.3 Choline (mg) 53 7.8 39.6 Inositol (mg) 30 4.4 22.4

[0074] Control formula ingredients: corn maltodextrin, caseinhydrolysate (enzymatically hydrolyzed and charcoal treated), sucrose,high oleic safflower oil, fractionated coconut oil (medium-chaintriglycerides), soy oil, diacetyl tartaric acid esters of mono- anddiglycerides, calcium phosphate tribasic, potassium citrate, mono- anddiglycerides, calcium carbonate, magnesium chloride, ascorbic acid,L-cystine dihydrochloride, sodium chloride, potassium chloride,L-tyrosine, choline chloride, L-tryptophan, ferrous sulfate, taurine,m-inositol, ascorbyl palmitate, vitamin E acetate, zinc sulfate, mixedtocopherols, L-carnitine, niacinamide, calcium pantothenate, cupricsulfate, vitamin A palmitate, thiamine chloride hydrochloride,riboflavin, pyridoxine hydrochloride, folic acid, potassium iodide,manganese sulfate, phylloquinone, biotin, sodium selenite, vitamin D₃,cyanocobalamin.

[0075] Formulas B, C and D Ingredients: corn maltodextrin, caseinhydrolysate (enzymatically hydrolyzed and charcoal treated), sucrose,high oleic safflower oil, fractionated coconut oil (medium-chaintriglycerides), soy oil, diacetyl tartaric acid esters of mono- anddiglycerides, calcium phosphate tribasic, potassium citrate, xanthangum, mono and diglycerides, calcium carbonate, magnesium chloride,ascorbic acid, L-cystine dihydrochloride, sodium chloride, potassiumchloride, L-tyrosine, choline chloride, L-tryptophan, ferrous sulfate,taurine, m-inositol, ascorbyl palmitate, vitamin E acetate, zincsulfate, mixed tocopherols, L-carnitine, niacinamide, calciumpantothenate, cupric sulfate, vitamin A palmitate, thiamine chloridehydrochloride, riboflavin, pyridoxine hydrochloride, folic acid,potassium iodide, manganese sulfate, phylloquinone, biotin, sodiumselenite, vitamin D₃, cyanocobalamin. TABLE 8A AMOUNT OF XANTHAN GUM(MG) IN CONTROL AND FORMULAS B, C, AND D Formula Per Liter Per 100 kcalPer 100 g Powder A 0 0 0 B 500 74 374 C 1,000 148 748 D 1,500 222 1,122

[0076] TABLE 9 Number Of Stools Per Day, Mean Rank Stool Consistency,And Percent Of Watery, Loose/Mushy, Soft And Formed Stools DuringBaseline and Experimental Periods¹ Baseline Experimental ParameterGroup/Formula (Days 1-7) (Days 1-8) Stools (number/day) Control  2.7 ±0.2  2.7 ± 0.2 B  2.6 ± 0.3  1.6 ± 0.2 C  2.6 ± 0.3  1.9 ± 0.2 D  2.5 ±0.3  2.1 ± 0.3 Mean Rank Stool Control  2.5 ± 0.1  2.1 ± 0.1Consistency² B  2.4 ± 0.1  2.0 ± 0.1 C  2.3 ± 0.1  2.3 ± 0.1 D  2.3 ±0.1  2.3 ± 0.1 % Watery Stools Control  6.9 ± 2.3 29.0 ± 6.1 B  8.9 ±2.7 22.6 ± 5.4 C 13.2 ± 3.6 11.0 ± 4.3 D 11.6 ± 2.7 14.2 ± 4.2 %Loose/Mushy Stools Control 41.6 ± 5.1 42.1 ± 5.5 B 47.7 ± 5.3 51.9 ± 6.3C 49.1 ± 5.4 51.3 ± 7.2 D 52.6 ± 4.3 42.6 ± 6.2 % Soft Stools Control45.4 ± 5.4 22.6 ± 4.9 B 38.0 ± 5.4 25.4 ± 6.3 C 31.6 ± 5.0 33.8 ± 7.5 D31.8 ± 4.0 37.0 ± 5.8 % Formed Stools Control  5.7 ± 1.9  6.3 ± 3.2 B 5.3 ± 1.9  0.0 ± 0.0 C  5.8 ± 2.7  2.2 ± 1.4 D  3.4 ± 1.2  5.4 ± 2.3

[0077] TABLE 10 Number Of Feedings Per Day, Average Intake, and Percentof Feeding With Spit Up, Vomiting And Spit Up And Vomiting DuringBaseline And Experimental Periods¹ Baseline Experimental ParameterGroup/Formula (Days 1-7) (Days 1-8) Number of feedings/day Control  7.5± 0.2  7.3 ± 0.3 B  7.4 ± 0.2  7.3 ± 0.3 C  7.4 ± 0.3  7.1 ± 0.3 D  7.2± 0.2  6.9 ± 0.2 Average Intake (ml/day) Control 524 ± 19 568 ± 26 B 556± 28 624 ± 32 C 525 ± 21 605 ± 24 D 551 ± 26 608 ± 21 % Feedings withSpit Up Control 11.1 ± 2.0 13.3 ± 3.5 B 17.0 ± 3.1 11.7 ± 2.1 C 23.8 ±4.3 15.0 ± 4.2 D 11.5 ± 2.2  9.0 ± 1.8 % of Subjects with any Control 8.2 ± 2.9  2.0 ± 1.0 Vomiting B  4.1 ± 1.4  3.9 ± 2.9 C  7.3 ± 2.6  3.6± 2.0 D  4.8 ± 1.6  2.6 ± 1.0 % of Feedings with Spit Up Control 19.3 ±3.5 15.3 ± 3.5 or Vomit B 21.0 ± 3.8 15.6 ± 3.3 C 31.2 ± 5.1 18.6 ± 4.5D 16.3 ± 3.2 11.5 ± 2.3

[0078] TABLE 11 Weight Gain Of Infants During The Baseline AndExperimental Periods¹ Baseline Experimental Parameter Group/Formula(Days 1-7) (Days 8-14) Weight Gain (grams/day) Control² 30.2 ± 2.7 31.1± 2.9 B³ 33.6 ± 2.6 34.4 ± 2.1 C⁴ 29.3 ± 2.8 30.9 ± 2.8 D⁵ 26.6 ± 2.434.1 ± 2.7

[0079] TABLE 12 Subject Outcome By Feeding (n = 182) Formula Exit StatusControl B C D Successful Completion 29 33 28 35 Early Exit (Days 8-14)¹ 8  2  0  2 Baseline Exit (Days 1-7)  9 11 17  8 Percentage of Exits² 22 6  0  5 Total 46 46 45 45

What is claimed is:
 1. A pediatric formula comprising, based on a 100kcal basis: about 8 to about 16 grams carbohydrate, about 3 to about 6grams lipid, about 1.8 to about 3.3 grams protein, and a toleranceimprover comprising an appropriate quantity of xanthan gum to produce aviscosity of no greater than about 200 centipoise, at a pH of 4.0, orless.
 2. A pediatric formula as defined in claim 1 having a viscosity ofno greater than about 175 centipoise.
 3. A pediatric formula as definedin claim 1 having a viscosity of no greater than about 100 centipoise.4. A pediatric formula as defined in claim 1 wherein the carbohydratecomprises from about 9.4 to about 12.3 grams.
 5. A pediatric formula asdefined in claim 1 wherein the lipid comprises from about 4.7 to about5.6 grams.
 6. A pediatric formula as defined in claim 1 wherein theprotein comprises from about 2.4 to about 3.3 grams.
 7. A pediatricformula as defined in claim 1 further comprising vitamins and minerals.8. A pediatric formula as defined in claim 1 wherein the vitamins andminerals are selected from the group consisting of calcium, phosphorus,sodium, chloride, magnesium, manganese, iron, copper, zinc, selenium,iodine, Vitamins A, E, C, D, K and the B complex, and mixtures thereof.9. A pediatric formula as defined in claim 1 wherein the lipid isselected from the group consisting of coconut oil, soy oil, corn oil,olive oil, safflower oil, high oleic safflower oil, MCT oil (mediumchain triglycerides), sunflower oil, high oleic sunflower oil, palm oil,palm olein, canola oil, lipid sources of arachidonic acid anddocosahexaneoic acid, and mixtures thereof.
 10. A pediatric formula asdefined in claim 1 wherein the protein comprises intact protein selectedfrom the group consisting of soy based protein, milk based protein,casein protein, whey protein, rice protein, beef collagen, pea protein,potato protein, and mixtures thereof.
 11. A pediatric formula as definedin claim 1 wherein the protein comprises hydrolyzed protein selectedfrom the group consisting of soy protein hydrolysate, casein proteinhydrolysate, whey protein hydrolysate, rice protein hydrolysate, potatoprotein hydrolysate, fish protein hydrolysate, egg albumen hydrolysate,gelatin protein hydrolysate, a combination of animal and vegetableprotein hydrolysates, and mixtures thereof.
 12. A pediatric formula asdefined in claim 1 wherein the protein comprises free amino acidsselected from the group consisting of L-tryptophan, L-tyrosine,L-cystine, L-taurine, L-methionine, L-arginine, and L-carnitine, andmixtures thereof.
 13. A pediatric formula as defined in claim 1 whereinthe carbohydrate is selected from the group consisting of hydrolyzed,intact, natural and chemically modified starches sourced from corn,tapioca, rice or potato in waxy or non waxy forms; sugars such asglucose, fructose, lactose, sucrose, maltose, high fructose corn syrup;and mixtures thereof.
 14. A pediatric formula as defined in claim 1further comprising a stabilizer, selected from the group consisting ofgum arabic, gum ghatti, gum karaya, gum tragacanth, agar, furcellaran,guar gum, gellan gum, locust bean gum, pectin, low methoxyl pectin,gelatin, microcrystalline cellulose, CMC, methylcellulose hydroxypropylmethyl cellulose, hydroxypropyl cellulose, dextran, carrageenans, andmixtures thereof.
 15. A pediatric formula in a powdered form whichcomprises, based on 100 grams of powder, about 30 to about 90 gramscarbohydrate, about 15 to about 30 grams lipid, about 8 to about 17grams protein, and an appropriate quantity of xanthan gum to produce aviscosity of no greater than about 200 centipoise at a pH of 4.0, orless, when diluted to a concentration suitable for pediatricconsumption.
 16. A method for providing nutrition to pediatric patientscomprising administering an effective amount of a pediatric formulacomprising, based on a 100 kcal basis: about 8 to about 16 gramscarbohydrate, about 3 to about 6 grams lipid, about 1.8 to about 3.3grams protein, and a tolerance improver comprising an appropriatequantity of xanthan gum to produce a viscosity of no greater than about200 centipoise at a pH of 4.0, or less.
 17. A method for providingnutrition to pediatric patients comprising administering an effectiveamount of a pediatric formula reconstituted from a powdered compositionwhich comprises, based on 100 grams of powder, about 30 to about 90grams carbohydrate, about 15 to about 30 grams fat, about 8 to about 17grams protein, and an appropriate quantity of xanthan gum to maintain aviscosity of no greater than about 200 centipoise at a pH of 4.0, orless.
 18. A method of improving tolerance in pediatric patientscomprising administering an effective amount of a pediatric formulareconstituted from a powdered composition which comprises, based on 100grams of powder, about 30 to about 90 grams carbohydrate, about 15 toabout 30 grams fat, about 8 to about 17 grams hydrolysate protein, and asufficient quantity of xanthan gum to produce a viscosity of no greaterthan about 200 centipoise at a pH of 4.0, or less.